Antiallergic properties of an orally effective agent,((3-(1H-tetrazol-5-yl)-phenyl)amino) oxoacetic acid n-butyl ester.

Agata, Mitsuji; Gotô, Hiroshi; Tsuriya, Yoshihiro; Tachibana, Kanta; Kuroda, Toshio

doi:10.1254/jjp.32.689

Cited by 5 publications

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Oxamates derived from 5‐aminopyrazoles

Peet

1986

Journal of Heterocyclic Chem

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Several oxamates were prepared from ethyl oxalyl chloride and 5-amino-4-cyanopyrazoles substituted in the 1-position with aryl, aroyl and arylsulfonyl groups. Both aroyl and arylsulfonyl groups suffered chlorideinduced cleavage during this process. The synthesis of 7-(6-chloro-3-pyridazinyl)-7H-pyrazolo[3,4-~-1,2,3-triazin-4(3H)-one (11) and its reaction with methanol to give 1-(6-chloro-3-pyridazinyl~5~methoxy-1H-pyrazole~4~ carboxamide (12) are also reported. A mechanism for this interesting transformation is presented. J. Heterocyclic Chem., 23, 193 (1986).There has been a great deal of recent interest in alkyl oxamates and oxamic acids or their salts as anti-allergy agents. Representative alkyl oxamates which reached later stages of drug development include Lodoxamide Ethyl (U-42,718) [1,2], WY-16,922 [3], AY-25,674 [4,5] and MTB [6]. Examples of oxamic acids and oxamic acid salts are 195 [7,8] and Lodoxamide Tromethamine (U-42,-585E) [9], respectively. Some of these agents have undergone extensive clinical evaluation. Q 00 II II NHCCOCH2CH3 0 AY -2 5 ~ 6 7 4 R" aR' NHCCOR ;fl R = H, R ' = CN, R" = NHCH3; WY-41,195 R = CH2CH3, R ' R = n-Bu, R ' = H , R" = 5 -1 e 1 r o r o 1 y 1 , M T B CONH2, A " = OCH3, WY-16,922 F N 00 fJ 00 II II NHCCOR II II ROCCNH C I R = C H 2 C H~, Lodoromide E t h y l ( U -4 2 , 7 1 8 ) R = NH3C(CH20H)3, Lodorarnide Tromslhorn!ne (U-42,585€)Most of these agents derive from anilines, and hence are also referred to as oxanilic acid derivatives [lo]. We decided to prepare oxamates of aminopyrazoles of the following general structure, in which the cyano group is ortho to R I R i OIhyI R I = a f y l , aroyl, ofylsulfonyl R4 = cyano the oxamate functionality. An ortho relationship of cyano and carboxamide groups to oxamate functionality is pre-193 sent in WY 922, respectively. A feature of the planned oxamates, not present in any of the existing oxamates with anti-allergic activity, was the electron-rich character of the aromatic (pyrazole) ring. It has been suggested that with Lodoxamide-like compounds, electronwithdrawing substituents on the aromatic ring are necessary for optimal activity [l]. A primary objective of the present study, then, was to explore the effect of an electronrich aromatic nucleus on the biological activity of oxamates.Two literature references exist on oxamates derived from aminopyrazoles. One described dioxamate 1, which was prepared from 4,5-diamino-lH-pyrazole and excess dimethyl oxalate, in a study describing lH-pyrazolo[3,4-h]pyrazines as purine antagonists [13]. The other describes 3-[(5-nitro-2-imidazolyl)pyrazol-5-yl)oxamic acid derivatives 2a-e as antibacterial agents [14]. I H 20. R =OCH3 b , R =OCH2CH3 C, R = OCgH5 d, R = NHNH2 8, R = NHOH Scheme I

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